Structural and Functional Impact of SRP54 Mutations Causing Severe Congenital Neutropenia

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Influence of visual targets and landmarks on honey bee foraging and waggle dancing

Animals use diverse sensory stimuli to navigate their environment and to recognize rewarding food sources.Honey bees use visual atributes of the targeted food source,such as its color,shape,size,direction and distance from the hive,and the landmarks around it to navigate during foraging.They transmit the location information of the food source to other bees if it is highly rewarding.To investigate the relative importance of these attributes,we trained bees to feeders in two different experiments.In the first experiment,we asked whether bees prefer to land on(a)a similar feeder at a different distance on the same heading or on(b)a visually distinct feeder located at the exact same location.We found that,within a short foraging range,bees relied heavily on the color and the shape of the food source and to a lesser extent on its distance from the hive.In the second experiment,we asked if moving the main landmark or the feeder(visual target)influenced recruitment dancing for the feeder.We found that foragers took longer to land and danced fewer circuits when the location of the food source,or a major landmark associated with it,changed.These results demonstrate that prominent visual atributes of food sources and landmarks are evidently more reliable than distance information and that foraging bees heavily utilize these visual cues at the later stages of their journey.     

OCC-1D regulates Wnt signaling pathway: potential role of long noncoding RNA in colorectal cancer

Molecular Biology Reports - Aberrant activation of the Wnt signaling pathway is observed in most colorectal cancers (CRC). OCC-1D is a splice variant of OCC-1 gene which is considered as a long...     

Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative,Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA

Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital Sequencing^TM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient’s cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing.     

Temporal variation of Bistorta vivipara‐associated ectomycorrhizal fungal communities in the High Arctic

Ectomycorrhizal (ECM) fungi are important for efficient nutrient uptake of several widespread arctic plant species. Knowledge of temporal variation of ECM fungi, and the relationship of these patterns to environmental variables, is essential to understand energy and nutrient cycling in Arctic ecosystems. We sampled roots of Bistorta vivipara ten times over two years; three times during the growing‐season (June, July and September) and twice during winter (November and April) of both years. We found 668 ECM OTUs belonging to 25 different ECM lineages, whereof 157 OTUs persisted throughout all sampling time‐points. Overall, ECM fungal richness peaked in winter and species belonging to Cortinarius, Serendipita and Sebacina were more frequent in winter than during summer. Structure of ECM fungal communities was primarily affected by spatial factors. However, after accounting for spatial effects, significant seasonal variation was evident revealing correspondence with seasonal changes in environmental conditions. We demonstrate that arctic ECM richness and community structure differ between summer (growing‐season) and winter, possibly due to reduced activity of the core community, and addition of fungi adapted for winter conditions forming a winter‐active fungal community. Significant month × year interactions were observed both for fungal richness and community composition, indicating unpredictable between‐year variation. Our study indicates that addressing seasonal changes requires replication over several years.     

Thermal Unfolding Pathway of PHD2 Catalytic Domain in Three Different PHD2 Species: Computational Approaches

Prolyl hydroxylase domain 2 containing protein (PHD2) is a key protein in regulation of angiogenesis and metastasis. In normoxic condition, PHD2 triggers the degradation of hypoxia-inducible factor 1 (HIF-1α) that induces the expression of hypoxia response genes. Therefore the correct function of PHD2 would inhibit angiogenesis and consequent metastasis of tumor cells in normoxic condition. PHD2 mutations were reported in some common cancers. However, high levels of HIF-1α protein were observed even in normoxic metastatic tumors with normal expression of wild type PHD2. PHD2 malfunctions due to protein misfolding may be the underlying reason of metastasis and invasion in such cases. In this study, we scrutinize the unfolding pathways of the PHD2 catalytic domain’s possible species and demonstrate the properties of their unfolding states by computational approaches. Our study introduces the possibility of aggregation disaster for the prominent species of PHD2 during its partial unfolding. This may justify PHD2 inability to regulate HIF-1α level in some normoxic tumor types.     

Fine root foraging strategies in Norway spruce forests across a European climate gradient

Fine root acclimation to different environmental conditions is crucial for growth and sustainability of forest trees. Relatively small changes in fine root standing biomass (FRB), morphology or mycorrhizal symbiosis may result in a large change in forest carbon, nutrient and water cycles. We elucidated the changes in fine root traits and associated ectomycorrhizal (EcM) fungi in 12 Norway spruce stands across a climatic and N deposition gradient from subarctic‐boreal to temperate regions in Europe (68°N–48°N). We analysed the standing FRB and the ectomycorrhizal root tip biomass (EcMB, g m^?2) simultaneously with measurements of the EcM root morphological traits (e.g. mean root length, root tissue density (RTD), N% in EcM roots) and frequency of dominating EcM fungi in different stands in relation to climate, soil and site characteristics. Latitude and N deposition explained the greatest proportion of variation in fine root traits. EcMB per stand basal area (BA) increased exponentially with latitude: by about 12.7 kg m^?2 with an increase of 10° latitude from southern Germany to Estonia and southern Finland and by about 44.7 kg m^?2 with next latitudinal 10° from southern to northern Finland. Boreal Norway spruce forests had 4.5 to 11 times more EcM root tips per stand BA, and the tips were 2.1 times longer, with 1.5 times higher RTD and about 1/3 lower N concentration. There was 19% higher proportion of root tips colonized by long‐distance exploration type forming EcM fungi in the southern forests indicating importance of EcM symbiont foraging strategy in fine root nutrient acquisition. In the boreal zone, we predict ca. 50% decrease in EcMB per stand BA with an increase of 2 °C annual mean temperature. Different fine root foraging strategies in boreal and temperate forests highlight the importance of complex studies on respective regulatory mechanisms in changing climate.     

Bioaccumulation of Trace Elements in Trophic Levels of Wetland Plants and Waterfowl Birds

Present study investigates relationships between total and bioaccessibility of trace elements (Cd, Co, Cr, Cu, Mn, NI, Pb, V, and Zn) concentrations in sediment and their bioaccumulation in species in Shadegan wetland in southwest of Iran. Bioavailability factor (BAF) and translocation factor (TF) were calculated in plants and trophic transfer factor (TTF) was determined in bird species. For this purpose, sampling of sediments, aquatic plants including Phragmites australis, Typha australis, Scripus maritimus and two bird species encircling Porphyrio porphyrio and globally threatened Marmaronetta angustirostris were carried out during winter 2009. Result of chemical analysis show that bioaccessibility concentrations of Mn (8.31 mg/kg), V (1.33 mg/kg), and Pb (1.03 mg/kg) are higher than other metals. The uptake trend of trace elements in plant decreases as root > stem > leaf. Accumulation levels of trace elements in different tissues of P. porphyrio and M. angustirostris are almost identical and considerable. Accumulation and toxicity of Cd in birds is more than plants. In addition, BAF of V, Pb, and Cr indicates high accumulation by plants and great pollution rate in the area of study. In S. maritimus TF for Mn, Cu, Pb, and V are high whereas in T. australis, Cu and Pb posses the highest TF. Also Cr, Co, Mn, Ni, and Zn have higher TF from stem to leaf than root to stem in P. australis. Finally, TTFs were compared in various bird species.